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Biomedical subjects

S Salmons

Publications and source records attributed to S Salmons.

At least 19 recordsLinked to original sources
PubMed1997

Relation between muscle contraction speed and hydraulic performance in skeletal muscle ventricles.

BACKGROUND: The fatigue resistance and power-to-weight ratio of skeletal muscle that has been conditioned by electrical stimulation makes cardiac assistance from a graft of such muscle a realistic prospect. A skeletal muscle must be surgically reconfigured to act on the circulating blood, but little is known about the power losses that accompany such interventions. We investigated in acute experiments the hydraulic performance of approximately cylindrical pumps made from sheep latissimus dorsi (LD) muscles, having first characterized the performance of each muscle in situ. METHODS AND RESULTS: Force-length and force-velocity relations were measured in situ for LD that had received either 8 weeks of stimulation at 2 Hz or no chronic stimulation. Two sizes of skeletal muscle ventricle (SMV) were formed from the same muscles, and their hydraulic performance was measured. The hydraulic performance was also calculated from the linear data, models of the force-length and force-velocity curves, and a description of the stress distribution within the SMV wall. The model predicted well the isovolumetric function of the ventricles and the optimum afterload but overestimated the flow and therefore the power. In conditioned ventricles the performance was particularly poor because of the slow contractile properties of the muscles. CONCLUSIONS: If SMVs are to pump effectively against the arterial impedance, the pressure drop caused by flow (or the internal resistance) should be lower than that of the ventricles we constructed. Progress can be made through refinement of surgical technique and stimulation protocols that generate faster fatigue-resistant muscles.

Animals↗
PubMed1997

Changes in nuclear protein composition in response to chronic electrical stimulation of skeletal muscle.

The adaptive response of skeletal muscle to increased functional demand involves phenotypic changes that affect contractile properties, energy metabolism and calcium kinetics. Some of these changes are known to be initiated at a pre-translational level, but the underlying regulatory mechanisms have not yet been identified. In this study we used chronic electrical stimulation (10 Hz, continuous) to initiate fast-to-slow muscle fibre-type transformation, and two-dimensional electrophoresis (2-DE) to assess changes in nuclear protein composition after 24 and 72 h. We report an early and sustained increase in the level of a 3 kDa protein in stimulated fast muscle (n = 6). The presence of the same protein in control slow muscle is consistent with a possible functional role in the determination of the slow phenotype.

Animals↗
PubMed1997

Intramural blood flow of skeletal muscle ventricles functioning as aortic counterpulsators.

BACKGROUND: Skeletal muscle ventricles (SMVs) working as aortic counterpulsators have provided long-term left ventricular assistance under experimental conditions. However, gradual deterioration of SMV pump function and rupture have been observed, and this may be related to compromised intramural blood flow during synchronized counterpulsation under systemic working conditions. METHODS: Transformed, double-layered SMVs in 6 sheep were stimulated for 3-minute periods (5 V, 30 Hz, burst duration and delay from QRS both 40% of the cardiac cycle) to work as diastolic counterpulsators in the systemic circulation at a 1:2 (SMV:heart) and 1:1 ratio, and on a mock circulation with low-pressure loading conditions at a 1:2 ratio. Thoracodorsal artery blood flow was monitored by ultrasonic flow probe, and intramural blood flow distribution was investigated by fluorescent microspheres. Thoracodorsal venous lactate concentrations were measured before and after each period of stimulation. RESULTS: Thoracodorsal artery blood flow increased significantly (p < 0.001) after stimulation. The magnitude of augmentation (89%; 95% confidence interval, 36% to 163%) was similar for all working conditions studied. Reactive hyperemia was observed after most 1:1 regimens but was rare after 1:2 regimens. A significant (p < 0.05) 15% increase in serum lactate levels was present after 1:1 regimens only. All regimens of stimulation resulted in a significant increase (p < 0.01) in blood flow to sections in the outer wall of the SMV, but a significant increase (p < 0.05) in blood flow to sections in the inner wall was observed only under low loading conditions. CONCLUSIONS: Skeletal muscle ventricles subjected to 1:1 systemic counterpulsation regimens work under partly anaerobic conditions. High loading conditions may compromise SMV inner wall blood flow.

Animals↗
PubMed1997

Flow in a simple model skeletal muscle ventricle: comparison between numerical and physical simulations.

Flow patterns generated during ventricular filling have been investigated for three different combinations of flow rate and injection volume. The numerical solutions from a commercially available computational fluid dynamics package were compared with observations made under identical flow conditions in a physical model for the purpose of code validation. Particle pathlines were generated from the numerical velocity data and compared with corresponding flow-visualization pictures. A vortex formed at the inlet to the ventricle in both cases: During the filling phase, the vortex expanded and traveled toward the apex of the ventricle until, at the end of filling, the vortex occupied the full radial extent of the ventricle; the vortex continued to travel once the filling process had ended. The vortices in vitro were more circular in shape and occupied a smaller volume than those generated by the numerical model. Nevertheless, comparison of the trajectories of the vortex centres showed that there was good agreement for the three conditions studied. Postprocessing of velocity data from the numerical solution yielded wall shear-stress measurements and particle pathlines that clearly illustrate the mass-transport qualities of the traveling vortex structure. For the cases considered here, the vortex transit produced a time-dependent shear stress distribution that had a peak value of 20 dynes cm-2, with substantially lower levels of shear stress in those regions not reached by the traveling vortex. We suggest that vortex formation and travel could reduce the residence time of fluid within a skeletal muscle ventricle, provided that the vortex travels the complete length of the ventricle before fluid is ejected at the start of the next cycle.

Blood Flow Velocity↗
PubMed1997

High-energy phosphates and tension production in rabbit tibialis anterior/extensor digitorum longus muscles.

The effects of repetitive muscle contraction on energy state and tension production were studied in rabbit tibialis anterior/extensor digitorum longus muscles that had been subjected to 90 days of continuous indirect electrical stimulation at 10 Hz. Anesthetized chronically stimulated and control rabbits were challenged with 15 min of stimulation at 4 and 15 tetani/min. Pi-to-phosphocreatine (PCr) ratio (Pi/PCr) was measured in vivo before, during, and after acute stimulation by 31P-magnetic resonance spectroscopy, and tension was recorded at the same time. Although Pi/PCr was low at rest, it was significantly higher in chronically stimulated muscle than in control muscle (0.20 +/- 0.02 vs. 0.05 +/- 0.01, P < 0.05). Stimulation of control muscle for 15 min at both 4 and 15 tetani/min induced a significant rise in Pi/PCr, whereas the same conditions in chronically stimulated muscle did not produce any significant departure from initial levels. The tension produced by control muscle fell to 93 +/- 3% of its initial value during stimulation at 4 tetani/min and to 61 +/- 7% at 15 tetani/min, respectively. In chronically stimulated muscle, on the other hand, tension was potentiated above its initial level at both stimulation rates (135 +/- 15 and 138 +/- 11%, respectively) and remained significantly elevated throughout each trial. The ability of chronically stimulated muscle to sustain high levels of activity with minimal perturbations in Pi/PCr or decrement in tension is attributable to cellular adaptations that include a well-documented increase in oxidative capacity.

Animals↗
PubMed1996

Fast-to-slow transformation in stimulated rat muscle.

Several previous studies have failed to demonstrate changes due to chronic stimulation in contractile speed of innervated fast rat muscles, and it has been suggested that the adaptive capacity of skeletal muscle in this species is limited. We have reassessed this contention. Fast muscles of the rat hind limb were stimulated continuously at 10 or 20 Hz for 55-61 days. The maximum shortening velocity of the extensor digitorum longus muscles was reduced to 50% of the control value. The proportion of type 1 fibers increased from 4% in control muscle to 34% in stimulated muscles and there was a corresponding reduction in type 2B/D fibers. The proportion of type 2A fibers after stimulation was similar to that in control muscles. These results, taken together with our published analyses of myosin isoform composition of these muscles, show that the mechanisms that control gene expression in response to activity are not exclusive to larger mammals.

Animals↗
PubMed1996

A novel video technique for visualizing flow structures in cardiovascular models.

We describe a video system that produces good quality images of particle trajectories in seeded fluid flows. The operation of a liquid crystal optical shutter and a modified charge-coupled device (CCD) camera were synchronized to generate images of particle trajectories which were stored in a framegrabber before being transferred to S-VHS tape. The camera system is particularly appropriate for visualizing transient or unsteady flows in models of the cardiovascular system as the integration time may be varied to produce particle trajectories of variable length.

Cardiac Output↗
PubMed1996

Formation and travel of vortices in model ventricles: application to the design of skeletal muscle ventricles.

Vortex-ring production was studied in axisymmetric elastomeric ventricles designed to stimulate flow in a cardiovascular assist device. A flow visualization technique was used to investigate the effects of reducing the inlet diameter and predilating the ventricle on vortex travel in two ventricles of different shape and size. In most cases, vortex rings formed during the filling phase. They were bounded by the incoming jet of fluid and the ventricular wall. The velocity of their centres during the filling period was proportional to the inflow velocity. During filling, vortex velocity was substantially independent of the shape and diameter of the two ventricles studied. It was dependent mainly on orifice diameter: a narrower inlet led to greater inflow velocities and proportionately greater vortex velocities. At the end of the filling phase, each vortex increased in size to occupy the full radial extent of the ventricle. This process was associated with a decrease in the axial velocity and strength of the vortex. At low flow rates, these losses resulted in the arrest of the vortex at end filling. Vortex motion in ventricles is particularly important in the design of a cardiovascular device such as the skeletal muscle ventricle (SMV), where small ejection fractions may leave blood at the apex of the ventricle relatively undisturbed. It is suggested that inlet diameter could be selected to favour the formation and travel of vortices, with a resultant reduction in apical residence time and hence a reduced risk of thrombus formation.

Coronary Circulation↗
PubMed1996

Pericardium-lined skeletal muscle ventricles: up to two years' in-circulation experience.

BACKGROUND: Skeletal muscle ventricles (SMVs) are autologous pumping chambers constructed from skeletal muscle. Skeletal muscle ventricular rupture and thromboembolism have complicated chronic models of this method of skeletal muscle cardiac assist. METHODS: The SMVs were constructed from the latissimus dorsi muscle in 10 dogs. The inner surface of each SMV was lined with autologous pericardium harvested at the time of SMV construction. After a 3-week period of vascular delay and 6 weeks of electrical conditioning to convert the muscle to a fatigue-resistant state, SMVs were connected to the descending thoracic aorta and stimulated to contract during cardiac diastole. RESULTS: Initial hemodynamics revealed that SMV contraction at 33 Hz increased diastolic pressure 24.7% (60.8 +/- 7.3 mm Hg versus 80.3 +/- 8.8 mm Hg). Skeletal muscle ventricle relaxation decreased presystolic pressure 14.4% (59.9 +/- 7.7 mm Hg versus 51.3 +/- 7.5 mm Hg) and decreased peak systolic pressure 4.1% (90.2 +/- 7.3 mm Hg versus 86.5 +/- 5.8 mm Hg). Hemodynamics were assessed at 1 to 2 weeks, then at 1, 2, 3, and 6 months, and at 6-month intervals thereafter. Hemodynamic performance remained stable for the duration of this study. After 2 years of pumping continuously in circulation, SMV contraction resulted in a 34.8% augmentation of diastolic pressure (63.6 +/- 6.6 mm Hg versus 85.3 +/- 6.4 mm Hg), a 17.2% decrease in presystolic pressure (54.7 +/- 3.73 mm Hg versus 45.3 +/- 4.1 mm Hg), and a 4.2% decrease in peak systolic pressure (95.3 +/- 10.4 mm Hg versus 91.3 +/- 12.3 mm Hg). Three dogs survived to 2 years with the SMVs in circulation. No animal showed evidence of thromboembolism during serial echocardiography or at autopsy and no SMVs ruptured. CONCLUSIONS: These data demonstrate that SMVs can provide effective hemodynamic assist over an extended period without specific complications related to the SMVs.

Animals↗
PubMed1996

Factors influencing vortex development in a model of a skeletal muscle ventricle.

A video technique was used to visualize flow patterns in a pulsatile model of a skeletal muscle ventricle (SMV). The shape and duration of SMV filling/emptying curves were determined by the stroke action of a computer-controlled piston pump. In this way we examined the effect of filling duration and injection volume on the flow structures. To simulate the interaction between the left ventricle and the SMV in the proposed clinical application, two filling/emptying regimes were employed with the period of each SMV cycle being either equal to or twice that of a typical cardiac cycle. Vortex formation at the inlet to the ventricle was a feature of both flow cycles during filling for all the combinations of injection volume and filling duration considered. When a pacing ratio of 1:1 was simulated, SMV filling was immediately followed by ejection, and the formed vortex was expelled. Under this flow regime, fluid in the apical end of the ventricle remained undisturbed. When the pacing ratio was 2:1, however, the quiescent period that followed filling allowed time for the formed vortex to travel a significant distance toward the apical end of the ventricle. Under certain conditions of injection volume and flow rate, the vortex reached the apex by the end of the quiescent period. We suggest that a ventricle connected to the aorta by a single, valveless conduit would require a flow regime that included a significant period of quiescence after filling. This would allow the vortex to reach and displace blood that would otherwise stagnate in the apex, thereby reducing the risk of thrombus formation.

Biomechanical Phenomena↗
PubMed1996

The use of coloured dye-extraction microspheres to measure blood flow in rabbit skeletal muscle: a validation study with special emphasis on repeated measurements.

We evaluated the use of coloured dye-extraction microspheres for measuring blood flow in the skeletal muscle of anaesthetized rabbits. Spheres were injected into the left atrium after sternotomy or lateral thoracotomy, or into the left ventricle via the left carotid artery. Both routes of administration produced adequate mixing of microspheres with the blood. In general, the values of flow obtained from spheres of different colour were well correlated. Resting flows were difficult to measure, owing to the low number of spheres and the correspondingly low absorption of the samples. Occlusion of the capillary bed by trapped spheres was less than 10% in both tibialis anterior and extensor digitorum longus muscles after injection of a total of 15 x 10(6) spheres. Injection via the left ventricle, a closed-chest procedure, gave a more stable preparation than injections via the left atrium. However, in both cases there was a progressive decline in hyperaemic muscle blood flow during a series of injections. These results indicate that it is possible to use this technique to measure skeletal muscle blood flow in the rabbit, but that it is difficult to exploit the advantages of sequential microsphere injection in this species.

Animals↗
PubMed1996

Induction of a fast-oxidative phenotype by chronic muscle stimulation: mechanical and biochemical studies.

We studied changes in the mechanical properties and myosin isoform composition of rabbit tibialis anterior muscles that were subjected to continuous stimulation at 2.5 Hz for up to 12 wk. The effects of stimulation at 2.5 Hz were less profound than those observed for the same duration of stimulation at 10 Hz (12). Stimulation at 10 Hz for 12 wk induced complete transformation to a slow-contracting muscle homogeneous in slow myosin isoforms; stimulation for the same period at 2.5 Hz resulted in moderate changes in contractile speed and a very small increase in the synthesis of slow myosin isoforms. On the other hand, the fatigue resistance of muscles stimulated at 2.5 Hz was as great, in both isometric and dynamic fatigue tests, as that of the muscles stimulated at 10 Hz. Thus entire fast skeletal muscles can be transformed to a state in which fast myosin isoforms continue to be synthesized, but the oxidative capacity is sufficient to support sustained working at a higher power output than that associated with slow muscle.

Animals↗
PubMed1996

Induction of a fast-oxidative phenotype by chronic muscle stimulation: histochemical and metabolic studies.

Chronic electrical stimulation of skeletal muscle at 10 Hz induces fast-to-slow fiber type transformation. Does a lower aggregate amount of activity lead to a less complete transformation, or does it produce the same transformation over a longer time course? We examined this question by subjecting adult rabbit tibialis anterior and extensor digitorum longus muscles to continuous stimulation at 2.5 Hz for 2-12 wk. Most of the fibers acquired the histochemical and immunocytochemical characteristics of type 2A, not type 1, fibers. There was a corresponding rise in oxidative activity, but this was accompanied by a marked decline in anaerobic glycolysis. The activities of hexokinase and 3-oxoacid CoA-transferase stopped increasing after 2 wk, glutamate oxaloacetate transaminase after 4 wk, and beta-hydroxyacyl-CoA dehydrogenase after 6 wk of stimulation. Succinate dehydrogenase, citrate synthase, lactate dehydrogenase, and creatine phosphokinase continued to change up to 12 wk of stimulation. Changes in enzyme activity were not as rapid or as marked as those observed for stimulation at 10 Hz, and none showed the typical two-phase response of oxidative enzyme activities to stimulation at 10 Hz. The latter may therefore be dependent on induction of type 1 myosin isoforms.

Anaerobiosis↗
PubMed1996

Increased contractile activity decreases RNA-protein interaction in the 3'-UTR of cytochrome c mRNA.

This study was designed to gain an insight into mechanisms by which cytochrome c gene expression is enhanced by increased contractile activity in skeletal muscle. When rat tibialis anterior muscles were stimulated (10 Hz, 0.25 ms) for 0, 2, 6, 12, or 24 h or 2, 5, 9, or 13 days (n = 4 for each time point), cytochrome c protein (enzyme-linked immunosorbent assay) and mRNA (Northern blot analysis) concentrations started to increase by 9 days, and this was associated with concurrent decreases in cytochrome c mRNA-protein interaction (RNA gel mobility shift assay). We found that the decreased RNA-protein interaction in the stimulated muscle extract was restored by ultracentrifugation (150,000 g, 1 h) in the supernatant fraction. The 150,000 g pellet fraction of stimulated muscle was capable of inhibiting the RNA-protein interaction in control tibialis anterior muscles. These results provide evidence of an inhibitory factor that is responsible for decreasing RNA-protein interaction in the 3'-untranslated region of cytochrome c mRNA in continuously stimulated muscle.

Animals↗
PubMed1996

Changes in ATP, phosphocreatine, and 16 metabolites in muscle stimulated for up to 96 hours.

Rabbit tibialis anterior muscles were stimulated continuously at 10 Hz for periods ranging from 2 min to 96 h and were analyzed for energy reserves and metabolic intermediates. Glycogen, ATP and phosphocreatine fell rapidly during the first 5 min of stimulation. Glycogen continued to fall to very low levels, whereas ATP and phosphocreatine rose, reaching 70% of control by 1 h, despite ongoing stimulation. After 2 h, glycogen also increased, regaining control levels in 4 days. Glucose rose to 4.5 times control in 30 min and still exceeded 2.5 times control at 24 h. In the first 2 min, glycolytic intermediates, glucose 6-phosphate (G-6-P), fructose 1,6-bisphosphate, lactate, and pyruvate more than doubled and then returned to control levels or below. Malate and 3-glycerophosphate rose 600 and 200%, respectively. Both of these compounds participate in shuttling reducing equivalents from cytoplasm into mitochondria. Citrate and alpha-ketoglutarate underwent much more modest changes. Glucose 1,6-bisphosphate (G-1,6-P2) fell to one-third of control by 2 h and then rose dramatically at 4 h. At 4 days it was still twice control. The 6-phosphogluconate (6PG) doubled at 2 min, then rose to 12 times control at 2 h, fell somewhat, and peaked at 16 times control at 24 h. Aspartate and alanine both exhibited a biphasic rise in concentration, whereas glutamate fell to 30% in 15 min and rose slowly after 4 h. The rise in glucose was interpreted to be the consequence of rapid glycogenolysis together with inhibition of hexokinase by G-1,6-P2 and elevated G-6-P. Paradoxically, glycogen resynthesis apparently occurred when the glycogen synthase stimulator, G-6-P, was very low, and the glycolysis stimulator, G-1,6-P2, was high. Although G-1,6-P2 is an inhibitor of 6PG dehydrogenase, the timing of the changes in G-1,6-P2 and 6PG levels suggests that the accumulation of 6PG was initiated by some other influence.

Adenosine Triphosphate↗
PubMed1995

The input-output relations of skeletal muscle.

We used three approaches to determine the stimulation patterns that maximize the isometric force-time integral per impulse (FTIpP) available from tibialis anterior muscles of the rabbit. Initially the interval between two pulses was fixed at the value that gave the maximum force-time integral, and successive pulses were added at intervals that maximized the FTIpP. We checked this iterative approach by a second method, in which a computer-generated protocol was used to deliver randomized bursts to the muscles. These experiments confirmed that optimal stimulation patterns for fast muscles consisted of an initial high-frequency portion followed by a train of impulses at a lower frequency. However, for muscles that had been stimulated chronically at a constant low frequency, an initial high-frequency portion conferred no advantage. In a third set of experiments we used constant-frequency bursts to generate contour surfaces that represented the dependence of FTIpP on the frequency and number of impulses. The results agreed with those from the earlier methods. We conclude that optimized patterns have potential for clinical use, but their value will depend strongly on the activation characteristics of the stimulated muscle.

Animals↗
PubMed1995

Increased muscle carnitine palmitoyltransferase II mRNA after increased contractile activity.

The capacity of skeletal muscle to oxidize fatty acids increases with endurance training. The oxidation of long-chain fatty acids occurs in mitochondria and is initiated by a carnitine-dependent transport step in which three enzymes help fatty acyl groups enter the matrix compartment. The purpose of this study was to determine whether pretranslational regulation of one of these three enzymes, carnitine palmitoyltransferase II (CPT II), as estimated from the level of CPT II mRNA, plays a role in the doubling of CPT activity in skeletal muscle of rats subjected to daily 2-h bouts of running on treadmills (P. A. Móle, L. B. Oscai, and J. O. Holloszy. J. Clin. Invest. 50: 2323-2330, 1971). After 100 min/day of running on motor-driven treadmills for 2 wk, CPT II mRNA in the plantaris muscle was unchanged when normalized per unit of extracted RNA but was 50% higher (P < 0.05) over sedentary controls when normalized per unit of muscle wet weight. To test whether additional contractile activity would make CPT II mRNA even higher, continuous indirect electrical stimulation was imposed on the tibialis anterior muscles. After 9 days of chronic stimulation, CPT II mRNA was 63, 221, and 137% greater than control (P < 0.001) when normalized to extracted RNA, muscle wet weight, and whole muscle, respectively, compared with the muscle in the control rats. These data indicate that pretranslational regulation of CPT II occurs in response to increased contractile activity in skeletal muscle.

Animals↗